HCV core, F, NS3, NS4B and NS5A are the major immunogenic proteins in humoral immunity in chronic HCV infection

Abstract number: 10.1111/j.1198-743X.2004.902_o356.x

Melen K.

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Hepatitis C virus (HCV) genome encodes for three structural (core, E1 and E2) and six nonstructural (NS2, NS3, NS4A, NS4B, NS5A and NS5B) as well as a recently identified F protein produced from an alternative reading frame from the core region. In order to study humoral immune responses against individual HCV proteins they were produced by baculovirus of Escherichia coli expression. The proteins were purified by preparative SDS-PAGE and antibody responses against different HCV proteins were analysed by quantitative Western blotting. The study material included serum specimens from 68 individuals chronically infected with HCV. All serum specimens were HCV RNA positive, and 21, 20, 23 and four individuals were of HCV genotypes 1, 2, 3 or 4, respectively. The core, F, NS3, NS4B and NS5A were the major antigenic proteins, and 97, 94, 68, 85 and 53% of the individuals had antibodies against these proteins, respectively. Lower rate of antibody positivity was observed also against E1, E2, NS4A and NS5B (428%) proteins, whereas NS2 protein appeared to be completely nonantigenic. As analysed by Western blotting the mean antibody levels were 430-fold higher against the core protein (mean titre 1:35 000) as compared with the other HCV proteins. Clearly detectable antibody levels were also observed against F (mean titre 1:1500), NS3 (1:4000), NS4B (1:9000) and NS5A (1:4500) proteins. No significant differences in antibody levels were seen in infections caused by different HCV genotypes. Follow-up of serum specimens from five individuals during a period of 2 years revealed that the antibody specificity and their levels remained remarkably constant in each individual. Our results indicate that baculo/ E. coli-produced HCV proteins are well suitable for diagnostic purposes and there is a tremendous variability in individual anti-HCV antibody levels and protein specificity.